Dietary Restriction

Created on Jan. 30, 2013, 6:52 p.m. by Hevok & updated by Hevok on May 18, 2013, 2:03 p.m.

Dietary Restriction

Dietary restriction (DR) by avoiding malnutrition robustly extends the Lifespan from yeast to rodents. DR is the only regimen that extends the Lifespan and healthspan in a spectrum of organisms including yeast, mice and nonhuman primates [Colman et al. 2009; Mattison et al. 2012; Weindruch et al. 1986].

Reducing the food consumption 25-60% without malnutrition extends the Lifespan of rodents up to 50% [Weindruch et al. 1986] and delays the onset of age-related maladies [Colman et al. 2009; Koubova & Guarante, 2003]. In mice and rats, DR can extend longevity by up to 50%, delay physiological Aging and postpone or diminish the morbidity of most age-related diseases [15885745]. DR elicits major metabolic reprogramming toward efficient fuel utilization and reduction in oxidative damage to macromolecules [Anderson & Weindruch, 2012; Sohal and Weindruch, 1996]. DR triggers global reprogramming of mitochondrial protein acetylome [Herbert et al. 2012].

A restricted diet lowers IGF1 levels, favors Apoptosis over cell proliferation and slows down tumor progression. Restoring normal ad libitum IGF1 levels in mice under DR abrogates the protective effect of DR on neoplastic progression [9354418].

Mice undergoing 40% DR from the age of 3 month exhibit a lower levels of Telomere shortening rate than those fed a normal diet. DR mice have therefore lower rates of chromosome anomalies. Mice that fed a lower caloric diet have a reduced incidence of Cancer as well as a lower incidence of other age-related illnesses such as osteoporosis, greater glucose uptake or improvements in motor coordination [23349740].

Mice engineered to produce produce more Telomerase (the protein that lengthens Telomeres and protects chromosomes enjoy an better health and live up to 20% longer. The significant increase in longevity is likely due to the protective effect against Cancer produced by DR as the Cancer incidence is 40% lower when compared with mice that overproduce Telomerase and have a normal diet [http://www.biocompare.com/life-science-news/129511-caloric-restriction-has-a-protective-effect-on-chromosomes/; http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053760] 23349740].

In long-lived wild derived Strains of mice the benefits of DR are less clear [17054664].

Whether DR also prolongs Lifespan in primates is questionable.

First studies in rhesus monkeys indicate a longer Lifespan, due to an overall reduced mortality [19590001]. However this was only true if censorship duo to non-age-related diseases was applied. Another study done by National Institute of Health (NIA) did not reveale any average Lifespan benefit from a 30% DR. DR improves some test results, but only in monkeys put on the diet when they were old. Still an effect on Maximum Lifespan remains unknown [http://www.nytimes.com/2012/08/30/science/low-calorie-diet-doesnt-prolong-life-study-of-monkeys-finds.html?_r=1] Mattison et al. 2012].

The Wisconsin monkeys got a much higher sucrose content in their food than the NIA animals. Wisconsin control animals could eat as much as they like, while the NIA control were given a set amount of food.

When done probably DR appears to confer health-benefits, such as lowering the risk of heart disease. People on DR have hearts that function more like those found in people two decades younger.

Still a severe restricted diet can lead to low Testosterone levels and problems with maintaining bone density in male individuals [http://online.wsj.com/article/SB10000872396390444772804577619394017185860.html].

Restricting your diet does not reduce the quality of live. Rodents under DR are usually more active on the physical and mental levels also into advanced ages. Volunteering people practicing DR report that they are much more concentrated. It is actually exactly the opposite eating too much reduces the quality of live, making you tired during the daytime period and cause problems sleeping well during the night-time.

DR in Humans

There are three evidence that DR works in humans:

  1. Okinawa
  2. Biosphere [Walford et al., 2002]
  3. Caloric restriction society - Fontana studies

Okinawa

First of all, inhabitants of Okinawa (an Japanese island) practice a DR-like lifestyle as part of their culture, are the longest-lived [Willcox et al., 2007a] and most disease-free population [Bernstein et al., 2004] on the globe. In fact, Okinawa has the highest prevalence of exceptionally long-lived individuals in the world [Willcox et al., 2006a]. Okinawa centenarians exhibit a high functional status throughout their 90s [Willcox et al., 2007b]. Okinawa has a high centenarian prevalence [Willcox et al., 2008a]. Okinawa centenarians have low plasma lipid peroxide implying protection against oxidative stress. Plasma lipid peroxide and vitamin E tocopherols were lower in okinawa centenarians, with the exception of intracellular Beta-tocopherol, which was higher. Tocopherol:cholesterol and tocopherol:LPO ratios were not different between age groups, although there were a correlation between α-Tocopherol and LPO in septuagenarians but not in centenarians (Suzuki et al., 2010). http://www.associatedcontent.com/article/3541/the_okinawa_diet_the_key_to_longevity.html

Epidemiological analysis on Okinawans found a low-caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low-risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum lifespan [Willcox et al., 2007a].

Okinawans centenarians had a lower plasma level of oxidized lipids and vitamin E-plasma levels, while intracellular β-tocopherols were higher (Suzuki et al., 2010).

Epidemiological evidence indicates that CR might have contributed to an extension of average and maximum lifespan and lowered risk for age-associated chronic diseases [Willcox et al., 2006b].

Biosphere 2

Secondly, the Biosphere 2 crew, who lived in isolation for two years, had a low-caloric diet and experienced many physiological, haematological, hormonal and biochemical (e.g. Insulin, T3 glucose and cholesterol decreased) changes, which resemble those of rodents and monkeys maintained on DR and remained in excellent health and high physical and mental activity [Walford et al., 2002]. Additional variations in several substances, not hitherto studied in DR-animals, like adrostenedione, thyroid binding globulin, renin, and transferrin were also observed [Walford et al., 2002].

Caloric Restriction Society

Thirdly, on-going studies on dietary restricting human volunteers (e.g. Caloric Restriction Society) already showed that it exerts beneficial effects on health and that, in particular, moderate protein restriction evokes similar adaptive responses as in dietary restricted rodents and monkeys [Fontana et al., 2008].

As DR works in almost all species tested so far, it would be really surprising if it would not work in humans. It is therefore hoped that research on DR will reveal which Factors in our diet are crucial for a healthy lifestyle. By making policy-makers aware of it, they could identify and define healthier diets. Further, understanding the actual mechanism underlying DR’s anti-ageing effect could lead to the identification of supplements or even development of pharmacological products mimicking the effect of DR without severe restricting one’s diet.

The aim is not just living longer, rather than being in an young and youthful state. Staying longer youthful and healthy is definitely not a wrong aim. Generally, a low-caloric, nutrient-dense, diversified diet low in fat and proteins (preferential mainly plant-derived) and without any extra added sugar is not a wrong lifestyle.

.. CALRIE study [Rochon et al., 2011]

CR decreases serum IGF1 (40%), protects against cancer and slows ageing in rodents. While severe CR without malnutrition did not change IGF1 and IGF:IGFBP3 ratio levels in humans, while total and free IGF1 were lower in moderately protein-restriction (1.67 to 0.95g/kg body weight per day) [Fontana et al., 2008].

.. Supplementation. giving as insights how and develop pharmacological products targeting age-related diseases

Caloric Intake

The usual recommended diet for adult males is about 2500 calories/day.

We do not yet know what the optimum of food intake is and which factors are most important to restrict and as you assumed these varies by species as well as strains.

The caloric intake if Okinawas was 1785 kcal/day [Willcox et al., 2007a], which is 15% and 40% less than the average of mainland Japanese (2068 kcal/day) and US (2980 kcal/day), respectively.

Biospherians consumed 30% less (from 2500 to 1784 kcal/day) for the first 6 month and then 2000 kcal/day for the remaining 12 months, which was combined with high level of physical activity of 70-80 h work/week [Walford et al., 1992].

Caloric Restriction Society members eat about 1800 kcal/day, which is 30% less than a typical Western diet [Holloszy and Fontana, 2007].

Ancient Monks

Ancient monks in India forest usually have their age > 100 years. Their reason for their longevity is probably due to dietary restriction, because they don’t eat after 12.00 a.m. They are also vegetarians. Essential amino acid rare in the plant.

Hormesis

DR extends median and maximal lifespan. It does it actually by slowing down ageing itself not just increasing survival or fitness. Starvation is the most extreme form of malnutrition and when permanently can seriously damage an organism. However, the DR response has some similarities to starvation and it was proposed that DR (i.e. low nutrient state) utilizes a low level of stress which enhances defences and repair systems. These beneficial effects of a low stress stimuli is conceptualised as “Hormesis”. Sequences of DR-essential genes do not vary across species, but rather than appear to be conserved. It is right that DR-essential genes are likely to change their activity under DR (i.e. become up- or downregulated). Upon DR, Insulin/IGF1/GH axis and TOR signalling are downregulated, while AMPK, Sirtuins and FOXOs become upregulated.

References

Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R (2012) Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489: 318-21.

Colman, R.J., Anderson, R.M., Johnson, S.C., Kastman, E.K., Kosmatka, K.J., Beasley, T.M., Allison, D.B., Cruzen, C., Simmons, H.A., Kemnitz, J.W., and Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204.

Mattison, J.A., Roth, G.S., Beasley, T.M., Tilmont, E.M., Handy, A.M., Herbert, R.L., Longo, D.L., Allison, D.B., Young, J.E., Bryant, M., et al. (2012). Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321.

Weindruch, R., Walford, R.L., Fligiel, S., and Guthrie, D. (1986). The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116, 641–654.

Anderson, R.M., and Weindruch, R. (2012). The caloric restriction paradigm: implications for healthy human aging. Am. J. Hum. Biol. 24, 101–106.

Koubova, J., and Guarente, L. (2003). How does calorie restriction work? Genes Dev. 17, 313–321.

Sohal, R.S., and Weindruch, R. (1996). Oxidative stress, caloric restriction, and aging. Science 273, 59–63.

Bernstein, A.M., Willcox, B.J., Tamaki, H., Kunishima, N., Suzuki, M., Willcox, D.C., Yoo, J.S., and Perls, T.T. (2004). First autopsy study of an Okinawan centenarian: absence of many age-related diseases. J Gerontol A Biol Sci Med Sci 59, 1195-1199.

Fontana, L., Weiss, E.P., Villareal, D.T., Klein, S., and Holloszy, J.O. (2008). Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7, 681-687.

Holloszy, J.O., and Fontana, L. (2007). Caloric restriction in humans. Exp Gerontol 42, 709-712.

Rochon, J., Bales, C.W., Ravussin, E., Redman, L.M., Holloszy, J.O., Racette, S.B., Roberts, S.B., Das, S.K., Romashkan, S., Galan, K.M., et al. (2011). Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. J Gerontol A Biol Sci Med Sci 66, 97-108.

Suzuki, M., Willcox, D.C., Rosenbaum, M.W., and Willcox, B.J. (2010). Oxidative stress and longevity in okinawa: an investigation of blood lipid peroxidation and tocopherol in okinawan centenarians. Curr Gerontol Geriatr Res 2010, 380460.

Walford, R.L., Harris, S.B., and Gunion, M.W. (1992). The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc Natl Acad Sci U S A 89, 11533-11537.

Walford, R.L., Mock, D., Verdery, R., and MacCallum, T. (2002). Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci 57, B211-224.

Willcox, B.J., Willcox, D.C., He, Q., Curb, J.D., and Suzuki, M. (2006a). Siblings of Okinawan centenarians share lifelong mortality advantages. J Gerontol A Biol Sci Med Sci 61, 345-354.

Willcox, B.J., Willcox, D.C., Todoriki, H., Fujiyoshi, A., Yano, K., He, Q., Curb, J.D., and Suzuki, M. (2007a). Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci 1114, 434-455.

Willcox, D.C., Willcox, B.J., He, Q., Wang, N.C., and Suzuki, M. (2008a). They really are that old: a validation study of centenarian prevalence in Okinawa. J Gerontol A Biol Sci Med Sci 63, 338-349.

Willcox, D.C., Willcox, B.J., Shimajiri, S., Kurechi, S., and Suzuki, M. (2007b). Aging gracefully: a retrospective analysis of functional status in Okinawan centenarians. Am J Geriatr Psychiatry 15, 252-256.

Willcox, D.C., Willcox, B.J., Todoriki, H., Curb, J.D., and Suzuki, M. (2006b). Caloric restriction and human longevity: what can we learn from the Okinawans? Biogerontology 7, 173-177.

Willcox, D.C., Willcox, B.J., Wang, N.C., He, Q., Rosenbaum, M., and Suzuki, M. (2008b). Life at the extreme limit: phenotypic characteristics of supercentenarians in Okinawa. J Gerontol A Biol Sci Med Sci 63, 1201-1208.

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Tags: restriction, cancer, Longevity, aging, longevity, lifespan, Aging, diet
Categories: News
Parent: Aging

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